Extracellular vesicles in the urine: markers and mediators of tissue damage and regeneration

Abstract

As in several body fluids, urine is a rich reservoir of extracellular vesicles (EVs) directly originating from cells facing the urinary lumen, including differentiated tubular cells, progenitor cells and infiltrating inflammatory cells. Several markers of glomerular and tubular damage, such as WT-1, ATF3 and NGAL, as well as of renal regeneration, such as CD133, have been identified representing an incredible source of information for diagnostic purposes. In addition, urinary extracellular vesicles (uEVs) appear to be involved in the cell-to-cell communication along the nephron, although this aspect needs further elucidation. Finally, uEVs emerge as potential amplifying or limiting factors in renal damage. Vesicles from injured cells may favour fibrosis and disease progression whereas those from cells with regenerative potential appear to promote cell survival. Here, we will discuss the most recent findings of the literature, on the light of the role of EVs in diagnosis and therapy for damage and repair of the renal tissue.

Keywords: biomarkers; exosomes; kidney injury; progenitor cells; urine.

Fig. 1.

uEVs mediate cell-to-cell communication and immunological functions within the nephron. The schematic picture shows the possible effects of uEVs in the intra-nephron communication. uEVs may provide an antioxidant effect in distal tubular cells when derived from tubular cells stimulated with anti-inflammatory mediators; or they may mediate the transfer of functional molecules, such as AQP2 to the recipient cells. In the bladder, uEVs may exert bacteriostatic and bacteriolytic effects by inhibiting bacteria adhesion to the bladder cells, blocking their growth or inducing their lysis.

Fig. 2.

EVs may amplify or limit renal damage. The schematic picture shows the cellular communication through uEVs in tubular cell damage. Ischaemic damage may induce fibroblast activation through the release of EVs from proximal tubular cells. Alternatively, upon cisplatin damage sensing, CD133⁺ progenitor cells may release EVs in order to protect the neighbouring tubular cells from damage.